Novel prospectives of Paeonia lactiflora root extract as a natural modulator of LPS-induced inflammation and collagen I synthesis in skin and oral gingival cells

Viktor Filatov^1*Alina Yarovaya²Egor Ilin²Elizaveta Patronova³Vadim Tashlitsky²Elena Kalenikova¹

• ¹Faculty of Fundamental Medicine, Lomonosov Moscow State University, Moscow, Russia
• ²Deparment of Chemistry, Lomonosov Moscow State University, Moscow, Russia
• ³Institute of Biomedical Systems and Biotechnology, Peter the Great St.Petersburg Polytechnic University, Saint Petersburg, Russia

Paeonia lactiflora Pall. (P. lactiflora) has long been used in traditional medicine for pain relief. Paeoniflorin as the main glucoside of P. lactiflora root extract could determine its pharmacological effects. Thus, the research was aimed at investigation of P. lactiflora root extract as a natural modulator of LPS-induced inflammation and I type collagen synthesis in skin and oral gingival cells. Transient receptor potential vanilloid 1 (TRPV1) channel and matrix metalloproteinases (MMPs) were chosen as the main targets for paeoniflorin in the P. lactiflora extract in silico. Maximum tolerated concentration was evaluated on keratinocytes as 0.5 mg/mL through MTT assay. In vitro study was conducted to determine the effects of P. lactiflora extract on LPS-induced inflammation and tissue destruction markers in skin keratinocytes, dermal and gingival fibroblasts using ELISA. Firstly, the standardized extract at concentrations of 0.03 mg/mL, 0.1 mg/mL and 0.5 mg/mL reduced TRPV1 amount in skin keratinocytes by 38.06%, 52.24% and 67.05% (P<0.001). Secondly, it was demonstrated that the extract at concentration of 0.5 mg/mL eliminated inflammatory stress induced by LPS reducing the production of TNF-α and production of IL-6 and IL-13 up to 25% (P<0.01) and 55% (P<0.001). Moreover, the extract demonstrated a protective effect on tissues destruction by reducing MMP-9 production by 70.27% in dermal fibroblasts and MMP-8 production by 39.32% in gingival fibroblasts (P<0.001). Furthermore, the extract restored I type collagen amount to initial level in dermal and gingival fibroblasts. Thus, P. lactiflora extract containing paeoniflorin is a promising natural modulator of LPS-induced inflammation in skin and oral gingival cells, providing complex protection against I type collagen destruction.